Varicella-zoster virus helicase-primase complex (VZV helicase-primase) (VZV helicase-primase)

The Varicella-zoster virus (VZV) helicase-primase complex is a heterotrimeric enzyme assembly essential for the replication of the VZV genome (PMID: 16141061). It consists of three subunits encoded by the viral genes ORF55 (helicase), ORF52 (primase), and ORF6 (primase-associated factor). This complex is responsible for unwinding double-stranded DNA and synthesizing RNA primers on the lagging strand during viral DNA synthesis. Unlike traditional nucleoside analogs such as acyclovir, which require phosphorylation by viral thymidine kinase, inhibitors of the helicase-primase complex act directly on the replication machinery (PMID: 22135105). This makes the complex an effective target for treating VZV infections, including herpes zoster (shingles), particularly in cases where resistance to standard therapies has developed. The drug amenamevir is a potent inhibitor of this complex that has been approved for clinical use in Japan, demonstrating the target's therapeutic relevance (PMID: 30136185). By halting the progression of the replication fork, these inhibitors effectively suppress viral shedding and accelerate the healing of skin lesions. The complex is highly conserved among alphaherpesviruses, providing a basis for the development of potent and specific antiviral agents.

Other names

VZV DNA helicase-primase complexORF55-ORF52-ORF6 complexHelicase-primase complex (VZV)Varicella-zoster virus DNA replication complex

The drugs act as non-nucleoside inhibitors that bind to the helicase-primase complex, preventing the ATP-dependent unwinding of DNA and the synthesis of RNA primers, thereby stopping viral DNA replication (PMID: 22135105).